Autoantibodies against nuclear proteins are not always but rather frequently present in sera of patients with primary biliary cirrhosis (PBC). The specificity and diagnostic value of these autoantibodies for PBC have only recently become clear through cloning of the cDNA of some of the corresponding autoantigens which allowed the establishment of immunological assays with recombinant autoantigens expressed in E. coli and eukaryotic cells. In this report we summarize primarily the knowledge on the structure and putative function of two nuclear autoantigens, the Sp100 and PML proteins, which are present in so-called nuclear dots (NDs) and against which autoantibodies are present in a subpopulation of PBC patients. Furthermore, the type of autoimmune response (epitope specificity and immunoglobulin class) against both the Sp100 and PML proteins and the specificity of the anti-Sp100 and anti-PML autoantibodies for PBC patients and patients with other autoimmune diseases is reviewed. Current knowledge clearly indicates that determination of anti-Sp100 and anti-PML autoantibodies substantially improves diagnosis of PBC as these autoantibodies are highly specific for this disease even when autoantibodies against mitochondrial antigens, a hallmark of most PBC patients, are not found. The type of autoimmune response against the Sp100 and PML proteins also provides some clues about possible mechanisms which lead to autoantigenicity of both proteins.